Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the...Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the activation of the protein kinase B/phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway.The purpose of this article is to elucidate how the downregulation of phosphatase and tensin homolog is involved in each key phase of optic nerve regeneration and to summarize the potential targets for therapeutic interventions in this process.Optic nerve regeneration progresses through five phases:stress response,growth navigation,nerve regeneration,synaptic reconstruction,and remyelination.During the stress response phase,the suppression of phosphatase and tensin homolog enhances the survival of retinal ganglion cells and promotes the proliferation of microglia.In the nerve regeneration phase,reduced levels of phosphatase and tensin homolog facilitate mitochondrial transport,while inhibition of the phosphatase and tensin homolog-L isoform specifically promotes mitophagy.During the synaptic reconstruction phase,the deletion of phosphatase and tensin homolog modulates the synthesis of axon extension-related proteins and stabilizes microglial microtubules,thereby accele rating the clearance of damaged synapses and the fo rmation of new ones.During the remyelination phase,the knockout of phosphatase and tensin homolog promotes the proliferation of oligodendrocyte progenitor cells and the diffe rentiation of oligodendrocytes,relieving myelination obstruction.This paper also discusses current strategies and translational challenges for neuron-specific inhibition of phosphatase and tensin homolog,including off-ta rget effects,delive ry precisio n,and long-term safety.By integrating molecular insights with emerging bioengineering approaches,this paper provides a framework for develo ping targeted therapies for optic nerve regeneration and broader applications in the field of central nervous system regeneration.展开更多
BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve outcomes.Large language models(LLMs)can potentially provide medical information for patients.AIM To examine the...BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve outcomes.Large language models(LLMs)can potentially provide medical information for patients.AIM To examine the performance of three LLMs,ChatGPT-3.5,ChatGPT-4.0,and Google Gemini,in answering HBV-related questions.METHODS LLMs’responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale,and disagreements were resolved by a third reviewer.Each question was run three times using three LLMs.Readability was assessed via the Gunning Fog index and Flesch-Kincaid grade level.RESULTS Overall,all three LLM chatbots achieved high average accuracy scores for subjective questions(ChatGPT-3.5:3.50;ChatGPT-4.0:3.69;Google Gemini:3.53,out of a maximum score of 4).With respect to objective questions,ChatGPT-4.0 achieved an 80.8%accuracy rate,compared with 62.9%for ChatGPT-3.5 and 73.1%for Google Gemini.Across the six domains,ChatGPT-4.0 performed better in terms of diagnosis,whereas Google Gemini demonstrated excellent clinical manifestations.Notably,in the readability analysis,the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight,far exceeding the reading level of the normal population.CONCLUSION Our results highlight the potential of LLMs,especially ChatGPT-4.0,for delivering responses to HBV-related questions.LLMs may be an adjunctive informational tool for patients and physicians to improve outcomes.Nevertheless,current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.展开更多
BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to in...BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.展开更多
Helicobacter pylori(H.pylori)infects approximately half of the population worldwide and causes chronic gastritis,peptic ulcers,and gastric cancer.Test-and-treat strategies have been recommended for the prevention of H...Helicobacter pylori(H.pylori)infects approximately half of the population worldwide and causes chronic gastritis,peptic ulcers,and gastric cancer.Test-and-treat strategies have been recommended for the prevention of H.pylori-associated diseases.Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal(GI)microbiota and its role in maintaining host homeostasis.Recently,an increasing number of studies have indicated that the colonization of H.pylori induces dramatic alterations in the gastric microbiota,with a predominance of H.pylori and a reduction in microbial diversity.Dysbiosis of the gut microbiome has also been observed after H.pylori infection,which may play a role in the development of colorectal cancer.However,there is concern regarding the impact of antibiotics on the gut microbiota during H.pylori eradication.In this review,we summarize the current literature concerning how H.pylori infection reshapes the GI microbiota and the underlying mechanisms,including changes in the gastric environment,immune responses,and persistent inflammation.Additionally,the impacts of H.pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed.The shifts in the GI microbiota and their crosstalk with H.pylori may provide potential targets for H.pylori-related gastric diseases and extragastric manifestations.展开更多
Diabetic wounds are among the most common complications of diabetes mellitus and their healing process can be delayed due to persistent inflammatory reactions,bacterial infections,damaged vascularization and impaired ...Diabetic wounds are among the most common complications of diabetes mellitus and their healing process can be delayed due to persistent inflammatory reactions,bacterial infections,damaged vascularization and impaired cell proliferation,which casts a blight on patients’health and quality of life.Therefore,new strategies to accelerate diabetic wound healing are being positively explored.Exosomes derived from mesenchymal stem cells(MSC-Exos)can inherit the therapeutic and reparative abilities of stem cells and play a crucial role in diabetic wound healing.However,poor targeting,low concentrations of therapeutic molecules,easy removal from wounds and limited yield of MSC-Exos are challenging for clinical applications.Bioengineering techniques have recently gained attention for their ability to enhance the efficacy and yield of MSC-Exos.In this review,we summarise the role of MSC-Exos in diabetic wound healing and focus on three bioengineering strategies,namely,parental MSC-Exos engineering,direct MSCExos engineering and MSC-Exos combined with biomaterials.Furthermore,the application of bioengineered MSC-Exos in diabetic wound healing is reviewed.Finally,we discuss the future prospects of bioengineered MSC-Exos,providing new insights into the exploration of therapeutic strategies.展开更多
基金National Natural Science Foundation of China,Nos.82260279,31960169the Natural Science Foundation of Jiangxi Province,Nos.20202ACB206002,20213BCJ22057a grant from School of Basic Medical Sciences,Nanchang University。
文摘Recent studies have found that the suppression of phosphatase and tensin homolog is one of the most effective single-gene approaches for promoting optic nerve regeneration.This effect is primarily mediated through the activation of the protein kinase B/phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway.The purpose of this article is to elucidate how the downregulation of phosphatase and tensin homolog is involved in each key phase of optic nerve regeneration and to summarize the potential targets for therapeutic interventions in this process.Optic nerve regeneration progresses through five phases:stress response,growth navigation,nerve regeneration,synaptic reconstruction,and remyelination.During the stress response phase,the suppression of phosphatase and tensin homolog enhances the survival of retinal ganglion cells and promotes the proliferation of microglia.In the nerve regeneration phase,reduced levels of phosphatase and tensin homolog facilitate mitochondrial transport,while inhibition of the phosphatase and tensin homolog-L isoform specifically promotes mitophagy.During the synaptic reconstruction phase,the deletion of phosphatase and tensin homolog modulates the synthesis of axon extension-related proteins and stabilizes microglial microtubules,thereby accele rating the clearance of damaged synapses and the fo rmation of new ones.During the remyelination phase,the knockout of phosphatase and tensin homolog promotes the proliferation of oligodendrocyte progenitor cells and the diffe rentiation of oligodendrocytes,relieving myelination obstruction.This paper also discusses current strategies and translational challenges for neuron-specific inhibition of phosphatase and tensin homolog,including off-ta rget effects,delive ry precisio n,and long-term safety.By integrating molecular insights with emerging bioengineering approaches,this paper provides a framework for develo ping targeted therapies for optic nerve regeneration and broader applications in the field of central nervous system regeneration.
基金Supported by National Natural Science Foundation of China,No.82260133the Key Laboratory Project of Digestive Diseases in Jiangxi Province,No.2024SSY06101Jiangxi Clinical Research Center for Gastroenterology,No.20223BCG74011.
文摘BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve outcomes.Large language models(LLMs)can potentially provide medical information for patients.AIM To examine the performance of three LLMs,ChatGPT-3.5,ChatGPT-4.0,and Google Gemini,in answering HBV-related questions.METHODS LLMs’responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale,and disagreements were resolved by a third reviewer.Each question was run three times using three LLMs.Readability was assessed via the Gunning Fog index and Flesch-Kincaid grade level.RESULTS Overall,all three LLM chatbots achieved high average accuracy scores for subjective questions(ChatGPT-3.5:3.50;ChatGPT-4.0:3.69;Google Gemini:3.53,out of a maximum score of 4).With respect to objective questions,ChatGPT-4.0 achieved an 80.8%accuracy rate,compared with 62.9%for ChatGPT-3.5 and 73.1%for Google Gemini.Across the six domains,ChatGPT-4.0 performed better in terms of diagnosis,whereas Google Gemini demonstrated excellent clinical manifestations.Notably,in the readability analysis,the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight,far exceeding the reading level of the normal population.CONCLUSION Our results highlight the potential of LLMs,especially ChatGPT-4.0,for delivering responses to HBV-related questions.LLMs may be an adjunctive informational tool for patients and physicians to improve outcomes.Nevertheless,current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.
基金supported by the National Natural Science Foundation of China(No.81960074)the Natural Science Foundation-Outstanding Youth Fund Project of Jiangxi Province(No.20232ACB216006)。
文摘BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.
基金funded by a grant of the National Natural Science Foundation of China(No.82260133).
文摘Helicobacter pylori(H.pylori)infects approximately half of the population worldwide and causes chronic gastritis,peptic ulcers,and gastric cancer.Test-and-treat strategies have been recommended for the prevention of H.pylori-associated diseases.Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal(GI)microbiota and its role in maintaining host homeostasis.Recently,an increasing number of studies have indicated that the colonization of H.pylori induces dramatic alterations in the gastric microbiota,with a predominance of H.pylori and a reduction in microbial diversity.Dysbiosis of the gut microbiome has also been observed after H.pylori infection,which may play a role in the development of colorectal cancer.However,there is concern regarding the impact of antibiotics on the gut microbiota during H.pylori eradication.In this review,we summarize the current literature concerning how H.pylori infection reshapes the GI microbiota and the underlying mechanisms,including changes in the gastric environment,immune responses,and persistent inflammation.Additionally,the impacts of H.pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed.The shifts in the GI microbiota and their crosstalk with H.pylori may provide potential targets for H.pylori-related gastric diseases and extragastric manifestations.
基金supported by grants from the National Natural Sciences Foundation of China(No.82160378,81460293)Chongqing Traditional Chinese Medicine Inheritance and Innovation Team Project(2023090006KJZX2022WJW008).
文摘Diabetic wounds are among the most common complications of diabetes mellitus and their healing process can be delayed due to persistent inflammatory reactions,bacterial infections,damaged vascularization and impaired cell proliferation,which casts a blight on patients’health and quality of life.Therefore,new strategies to accelerate diabetic wound healing are being positively explored.Exosomes derived from mesenchymal stem cells(MSC-Exos)can inherit the therapeutic and reparative abilities of stem cells and play a crucial role in diabetic wound healing.However,poor targeting,low concentrations of therapeutic molecules,easy removal from wounds and limited yield of MSC-Exos are challenging for clinical applications.Bioengineering techniques have recently gained attention for their ability to enhance the efficacy and yield of MSC-Exos.In this review,we summarise the role of MSC-Exos in diabetic wound healing and focus on three bioengineering strategies,namely,parental MSC-Exos engineering,direct MSCExos engineering and MSC-Exos combined with biomaterials.Furthermore,the application of bioengineered MSC-Exos in diabetic wound healing is reviewed.Finally,we discuss the future prospects of bioengineered MSC-Exos,providing new insights into the exploration of therapeutic strategies.
